Document Detail


Direct inhibition by angiotensin II of insulin-dependent glucose transport activity in mammalian skeletal muscle involves a ROS-dependent mechanism.
MedLine Citation:
PMID:  20384568     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
No previous study has investigated how the vaso-constrictive peptide Ang II impacts insulin action in isolated mammalian skeletal muscle. We investigated the molecular actions of Ang II on insulin signalling and glucose transport in skeletal muscle from lean Zucker rats. Soleus strips were incubated with insulin (5 mU/ml) and/or Ang II (500 nM) for 2 hours. Ang II caused significant (p < 0.05) inhibition of insulin-stimulated glucose transport (39%) and decreased phosphorylation of Akt Ser(473) (37%) and glycogen synthase kinase-3beta Ser(9) (42%) without affecting phosphorylation of IRS-1 Ser(307) or p38 MAPK. We used the superoxide dismutase mimetic, tempol (1 mM), to determine if reactive oxygen species (ROS) contribute to Ang II-mediated insulin resistance. Tempol partially reversed (42%) Ang II-induced inhibition of insulin-stimulated glucose transport. These results indicate that Ang II inhibits distal insulin signalling and insulin-stimulated glucose transport in isolated mammalian skeletal muscle, and that this effect is partially mediated by ROS.
Authors:
Maggie K Diamond-Stanic; Erik J Henriksen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Archives of physiology and biochemistry     Volume:  116     ISSN:  1744-4160     ISO Abbreviation:  Arch. Physiol. Biochem.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-27     Completed Date:  2010-07-21     Revised Date:  2012-03-15    
Medline Journal Info:
Nlm Unique ID:  9510153     Medline TA:  Arch Physiol Biochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  88-95     Citation Subset:  IM    
Affiliation:
Muscle Metabolism Laboratory, Department of Physiology and Arizona Diabetes Program, University of Arizona College of Medicine, Tucson, AZ 85721-0093, USA.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II / metabolism,  pharmacology*
Animals
Biological Transport
Female
Glucose / metabolism,  pharmacology
Hypoglycemic Agents / metabolism,  pharmacology
Insulin / metabolism*,  pharmacology
MAP Kinase Kinase Kinases
Mammals / metabolism
Muscle, Skeletal / drug effects,  metabolism
Phosphorylation / drug effects
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-akt / metabolism
Rats
Rats, Zucker
Reactive Oxygen Species / metabolism*,  pharmacology
Signal Transduction / drug effects
p38 Mitogen-Activated Protein Kinases / metabolism,  pharmacology
Grant Support
ID/Acronym/Agency:
DK063967/DK/NIDDK NIH HHS; R01 DK063967-01A2/DK/NIDDK NIH HHS; T32 HL07249/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Hypoglycemic Agents; 0/Insulin; 0/Proto-Oncogene Proteins; 0/Reactive Oxygen Species; 11128-99-7/Angiotensin II; 50-99-7/Glucose; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 2.7.11.25/MAP Kinase Kinase Kinases; EC 2.7.11.25/MAP3K8 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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